Human immunodeficiency viruses and various Plasmodium species have emerged to high prevalence in the same regions of the world Causing intense morbidity and mortality. We propose an experiment that will pilot development of a primate model of lentivirus and malaria parasite co-infection. The pattern of co- infection we will model is adults living in regions of the world, such as Southeast Asia, that are endemic for P. vivax malaria and are experiencing the most explosive increase in new HIV-1 infections. Our studies will combine well-established models of AIDS and malaria in rhesus macaques: 1) SIV, a lentivirus that establishes a severe immunodeficiency disease (simian AIDS, SAIDS) and 2) Plasmodium cynomolgi, which causes relapsing disease resembling malaria induced by P. vivax, the most wide-spread human Plasmodium species. The hypotheses underlying the proposed studies are that relapsing malaria induced by P. cynomolgi will alter the course of SAIDS and immune responses to SIV, and that immunosuppression by SIV will alter P, cynomolgi growth, relapse and immune responses to the malaria parasite. In Specific Aim I we propose to conduct a pilot study of co-infection with SIV and P. cynomolgi in rhesus macaques. The studies proposed in Specific Aim 2 will examine immunological parameters including lymphocyte subsets, chemokine and cytokine expression, and humoral and cellular immune responses to selected SIV and P. cynomolgi proteins to determine which, if any, of these parameters correlate with progression of SAIDS or P. cynomolgi relapsing malaria in co-infected or singly infected animals. Results of the proposed pilot experiment will direct further studies that may lead to strategies for improving health care of individuals in regions of the world where there are dual epidemics of AIDS and malaria.